ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.366T>G (p.Val122=) (rs190900046)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000494795 SCV000578280 likely benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics RCV000164590 SCV000215249 likely benign Hereditary cancer-predisposing syndrome 2014-10-23 criteria provided, single submitter clinical testing
GeneDx RCV000444743 SCV000516022 benign not specified 2015-06-29 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000458766 SCV000560292 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000444743 SCV000600341 likely benign not specified 2016-08-31 criteria provided, single submitter clinical testing
Color RCV000164590 SCV000688447 likely benign Hereditary cancer-predisposing syndrome 2017-09-11 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758817 SCV000887674 likely benign not provided 2018-02-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000444743 SCV000918726 uncertain significance not specified 2018-04-16 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.366T>G alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was observed with an allele frequency of 1.4e-05 in 277192 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (1.4e-05 vs 0.001), allowing no conclusion about variant significance. The variant, c.366T>G, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Cherdyntseva_2017). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign/benign." Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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